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This study explored how social media users' mocking of a public health campaign can affect other users' emotions, cognitions, and behavioral intentions. Inspired by public mocking of the CDC's "Say No to Raw Dough" campaign aiming to prevent food poisoning caused by eating raw flour-based products, this experiment ( N  = 681) employed a 2 (Public responses to a PSA: Mocking or serious) x 3 (Organizational response to public responses: Self-mocking, serious, or none) + 1 (control condition) design. Statistical tests revealed that user-generated mocking can lower intentions to avoid the health risk by decreasing perceptions of injunctive norms (that is, seeing others mock a public health campaign resulted in weaker perceptions that others think you should avoid the risky behavior). Mockery of a public health campaign also engender anger at the CDC and at other users, with the target of the anger having differential effects on intentions to avoid eating raw dough. Implications for theory and the practice of social media-based health promotion are discussed.

Despite effective countermeasures, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists worldwide because of its ability to diversify and evade human immunity. This evasion stems from amino acid substitutions, particularly in the receptor binding domain (RBD) of the spike protein that confers resistance to vaccine-induced antibodies and antibody therapeutics. To constrain viral escape through resistance mutations, we combined antibody variable regions that recognize different RBD sites into multispecific antibodies. Here, we describe multispecific antibodies, including a trivalent trispecific antibody that potently neutralized diverse SARS-CoV-2 variants and prevented virus escape more effectively than single antibodies or mixtures of the parental antibodies. Despite being generated before the appearance of Omicron, this trispecific antibody neutralized all major Omicron variants through BA.4/BA.5 at nanomolar concentrations. Negative stain electron microscopy suggested that synergistic neutralization was achieved by engaging different epitopes in specific orientations that facilitated binding across more than one spike protein. Moreover, a tetravalent trispecific antibody containing the same variable regions as the trivalent trispecific antibody also protected Syrian hamsters against Omicron variants BA.1, BA.2, and BA.5 challenge, each of which uses different amino acid substitutions to mediate escape from therapeutic antibodies. These results demonstrated that multispecific antibodies have the potential to provide broad SARS-CoV-2 coverage, decrease the likelihood of escape, simplify treatment, and provide a strategy for antibody therapies that could help eliminate pandemic spread for this and other pathogens.

Research has found that when a public figure discloses an illness, it can motivate members of the public to reconsider their own health behaviors, particularly when they have a parasocial relationship with the public figure. When the public figure is a politician, it is possible that partisan differences may also influence emotional, attentional, and behavioral responses to health news. We empirically examined public responses to Democrat John Fetterman's disclosure of his treatment for depression shortly after he was inducted into the United States Senate as the junior senator from Pennsylvania in 2023. Using a survey of adult Pennsylvania residents who identified as eligible voters in April 2023, we found that 204 respondents were aware of the news of Fetterman's diagnosis of and treatment for depression. Our data revealed that differences in demographics and parasocial relationships-both positive and negative-with Fetterman predicted different patterns of emotional responses to the news. In addition, age, anger, a negative parasocial relationship, and a positive parasocial relationship were associated with additional outcomes, including attention to news about the disclosure and depression-related information seeking. Mental health advocates could use politicians' depression disclosures to provide information at a time when people are paying more attention to the condition; however, they may need to find other public figures to counteract negative responses to partisan officials. Policymakers could also consider funding mental health campaigns, which could be launched alongside public figure disclosures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Myrick and Willoughby.)

The relative conservation of the influenza hemagglutinin (HA) stem compared to that of the immunodominant HA head makes the HA stem an attractive target for broadly protective influenza vaccines. Here we report the first-in-human, dose-escalation, open-label trial (NCT04579250) evaluating an unadjuvanted group 2 stabilized stem ferritin nanoparticle vaccine based on the H10 A/Jiangxi-Donghu/346/2013 influenza HA, H10ssF, in healthy adults. Participants received a single 20 mcg dose (n = 3) or two 60 mcg doses 16 weeks apart (n = 22). Vaccination with H10ssF was safe and well tolerated with only mild systemic and local reactogenicity reported. No serious adverse events occurred. Vaccination significantly increased homologous H10 HA stem binding and neutralizing antibodies at 2 weeks after both first and second vaccinations, and these responses remained above baseline at 40 weeks. Heterologous H3 and H7 binding antibodies also significantly increased after each vaccination and remained elevated throughout the study. These data indicate that the group 2 HA stem nanoparticle vaccine is safe and induces stem-directed binding and neutralizing antibodies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Bi-functional N-Hydroxysuccinimide (NHS) linkers are widely used in the conjugation processes linking an immunogen with a carrier protein capable of boosting immunity. A potential vaccine candidate against HIV-1, called fusion peptide (FP), is covalently linked to the recombinant tetanus toxoid heavy-chain fragment C (rTTHC) via this type of linker. A reversed-phase liquid chromatography (RPLC-UV) method was used to monitor the linker's degradation kinetics in various buffers, mimicking the steps in the conjugation process. The kinetics of the reactivities of the linkers are revealed in this study and can provide a good guidance to help effective conjugation process before these linkers are completely hydrolyze to the inactive degradants. Three cross-linkers degradation pathways were evaluated: Sulfosuccinimidyl (4-iodoacetyl) aminobenzoate (Sulfo-SIAB), PEGylated SMCC (SM(PEG) 2 ), and N-γ-maleimidobutyryl-oxysulfosuccinimide ester (Sulfo-GMBS). We have reported kinetics for Sulfo-SIAB., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Published by Elsevier B.V.)

Background: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum infection in a region where this organism is endemic is unclear., Methods: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis., Results: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons)., Conclusions: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.)., (Copyright © 2024 Massachusetts Medical Society.)

When celebrities, political figures, influencers, or anyone with a large following publicly disclose an illness or die, the news becomes a de facto public health campaign. Until health communicators began studying such disclosures and the effects of the following waves of media coverage, however, it was not known to what extent these events impacted the public. A growing body of research has empirically documented these events and examined the factors that predict which types of audiences are most affected and why. Beyond motivating research opportunities, celebrity and influencer health disclosures or deaths can impact calls to hotlines, views on health-related websites, discussions of related topics on social media, behavioral changes relevant to the disclosure, increased news coverage of celebrity health research, integration of celebrity health narratives into strategic health campaigns, and even policy changes. We provide an overview of research conducted in this area and detail examples of the impact that celebrity health disclosures and studies about those disclosures have had on public discourse and public health.

BACKGROUNDBroadly neutralizing monoclonal antibodies (bNAbs) represent a promising strategy for HIV-1 immunoprophylaxis and treatment. 10E8VLS and VRC07-523LS are bNAbs that target the highly conserved membrane-proximal external region (MPER) and the CD4-binding site of the HIV-1 viral envelope glycoprotein, respectively.METHODSIn this phase 1, open-label trial, we evaluated the safety and pharmacokinetics of 5 mg/kg 10E8VLS administered alone, or concurrently with 5 mg/kg VRC07-523LS, via s.c. injection to healthy non-HIV-infected individuals.RESULTSEight participants received either 10E8VLS alone (n = 6) or 10E8VLS and VRC07-523LS in combination (n = 2). Five (n = 5 of 8, 62.5%) participants who received 10E8VLS experienced moderate local reactogenicity, and 1 participant (n = 1/8, 12.5%) experienced severe local reactogenicity. Further trial enrollment was stopped, and no participant received repeat dosing. All local reactogenicity resolved without sequelae. 10E8VLS retained its neutralizing capacity, and no functional anti-drug antibodies were detected; however, a serum t1/2 of 8.1 days was shorter than expected. Therefore, the trial was voluntarily stopped per sponsor decision (Vaccine Research Center, National Institute of Allergy and Infectious Diseases [NIAID], NIH). Mechanistic studies performed to investigate the underlying reason for the reactogenicity suggest that multiple mechanisms may have contributed, including antibody aggregation and upregulation of local inflammatory markers.CONCLUSION10E8VLS resulted in unexpected reactogenicity and a shorter t1/2 in comparison with previously tested bNAbs. These studies may facilitate identification of nonreactogenic second-generation MPER-targeting bNAbs, which could be an effective strategy for HIV-1 immunoprophylaxis and treatment.TRIAL REGISTRATIONClinicaltrials.gov, accession no. NCT03565315.FUNDINGDivision of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

Novel, public behaviors, such as masking, should be susceptible to normative influence. This paper advances the theory of normative social behavior by considering a new set of moderators of normative influence - superdiffuser traits - and by clarifying the antecedents and consequences of exposure to collective norms. We use data from a two-wave survey of a cohort living in one U.S. county during the pandemic ( N  = 913) to assess normative effects on masking. We also used a bipartite network (based on people shopping for food in the same stores) to examine exposure to collective norms. The results show different superdiffuser traits have distinct effects on the relationship between perceived injunctive norms and masking intentions. Exposure to collective norms influences masking, but this influence depends on how people interact with their social environments. Network analysis shows that behavioral homophily is a significant predictor of selective exposure to collective norms earlier (but not later) in the pandemic. Implications for understanding normative influence in a context where opinion leadership matters are discussed.

Recent work by our laboratory and others indicates that co-display of multiple antigens on protein-based nanoparticles may be key to induce cross-reactive antibodies that provide broad protection against disease. To reach the ultimate goal of a universal vaccine for seasonal influenza, a mosaic influenza nanoparticle vaccine (FluMos-v1) was developed for clinical trial (NCT04896086). FluMos-v1 is unique in that it is designed to co-display four recently circulating haemagglutinin (HA) strains; however, current vaccine analysis techniques are limited to nanoparticle population analysis, thus, are unable to determine the valency of an individual nanoparticle. For the first time, we demonstrate by total internal reflection fluorescence microscopy and supportive physical-chemical methods that the co-display of four antigens is indeed achieved in single nanoparticles. Additionally, we have determined percentages of multivalent (mosaic) nanoparticles with four, three, or two HA proteins. The integrated imaging and physicochemical methods we have developed for single nanoparticle multivalency will serve to further understand immunogenicity data from our current FluMos-v1 clinical trial., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Human papillomavirus (HPV) vaccination rates are lower than other recommended adolescent vaccines. Cancer survivor narratives are used to promote cancer prevention and control, but little is known about their impact on adolescent HPV vaccination., Objective: This pilot study explored the feasibility and effects of a video education intervention using a cancer survivor narrative to improve parents' attitudes toward and intentions to get the HPV vaccine., Methods: This study utilized a one-group design; participants completed a pre-intervention survey, watched the video before attending their sons' wellness visits, and completed a post-intervention survey within one week of their appointment. Using the narrative persuasion framework, we developed a 4-minute video of a local HPV-related cancer survivor to promote the HPV vaccine as cancer prevention. We recruited 37 participants between June and October 2020. Participants were parents of males ages 9-17 who had not yet initiated HPV vaccination., Results: After the video, more parents agreed that HPV vaccination is safe (pre: 66% vs. post: 82%; P = .045) and that their child's chances of getting HPV-related cancer in the future are high (pre: 24% vs. post: 46%; P = .014). Overall, 91% of parents felt the cancer survivor story helped them understand the risks of HPV cancers, and 52% said the story influenced their decision to start HPV vaccination for their child., Conclusions: Our findings suggest that cancer survivor narratives influence parents' vaccine opinions and understanding of their child's risk of HPV infection, leading to increased parental intent to get the HPV vaccine for their adolescent males., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sudan Ebola virus can cause severe viral disease, with an average case fatality rate of 54%. A recent outbreak of Sudan Ebola virus in Uganda caused 55 deaths among 164 confirmed cases in the second half of 2022. Although vaccines and therapeutics specific for Zaire Ebola virus have been approved for use during outbreak situations, Sudan Ebola virus is an antigenically distinct virus with no approved vaccines available., Methods: In this phase 1, open-label, dose-escalation trial we evaluated the safety, tolerability, and immunogenicity of a monovalent chimpanzee adenovirus 3 vaccine against Sudan Ebola virus (cAd3-EBO S) at Makerere University Walter Reed Project in Kampala, Uganda. Study participants were recruited from the Kampala metropolitan area using International Review Board-approved written and electronic media explaining the trial intervention. Healthy adults without previous receipt of Ebola, Marburg, or cAd3 vectored-vaccines were enrolled to receive cAd3-EBO S at either 1 × 10 10 or 1 × 10 11 particle units (PU) in a single intramuscular vaccination and were followed up for 48 weeks. Primary safety and tolerability endpoints were assessed in all vaccine recipients by reactogenicity for the first 7 days, adverse events for the first 28 days, and serious adverse events throughout the study. Secondary immunogenicity endpoints included evaluation of binding antibody and T-cell responses against the Sudan Ebola virus glycoprotein, and neutralising antibody responses against the cAd3 vector at 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT04041570, and is completed., Findings: 40 healthy adults were enrolled between July 22 and Oct 1, 2019, with 20 receiving 1 × 10 10 PU and 20 receiving 1 × 10 11 PU of cAd3-EBO S. 38 (95%) participants completed all follow-up visits. The cAd3-EBO S vaccine was well tolerated with no severe adverse events. The most common reactogenicity symptoms were pain or tenderness at the injection site (34 [85%] of 40), fatigue (29 [73%] of 40), and headache (26 [65%] of 40), and were mild to moderate in severity. Positive responses for glycoprotein-specific binding antibodies were induced by 2 weeks in 31 (78%) participants, increased to 34 (85%) participants by 4 weeks, and persisted to 48 weeks in 31 (82%) participants. Most participants developed glycoprotein-specific T-cell responses (20 [59%, 95% CI 41-75] of 34; six participants were removed from the T cell analysis after failing quality control parameters) by 4 weeks after vaccination, and neutralising titres against the cAd3 vector were also increased from baseline (90% inhibitory concentration of 47, 95% CI 30-73) to 4 weeks after vaccination (196, 125-308)., Interpretation: The cAd3-EBO S vaccine was safe at both doses, rapidly inducing immune responses in most participants after a single injection. The rapid onset and durability of the vaccine-induced antibodies make this vaccine a strong candidate for emergency deployment in Sudan Ebola virus outbreaks., Funding: National Institutes of Health via interagency agreement with Walter Reed Army Institute of Research., Competing Interests: Declaration of interests NJS is listed on patents involving cAd3-vectored vaccines. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Mpox virus (MPXV) caused a global outbreak in 2022. Although smallpox vaccines were rapidly deployed to curb spread and disease among those at highest risk, breakthrough disease was noted after complete immunization. Given the threat of additional zoonotic events and the virus's evolving ability to drive human-to-human transmission, there is an urgent need for an MPXV-specific vaccine that confers protection against evolving MPXV strains and related orthopoxviruses. Here, we demonstrate that an mRNA-lipid nanoparticle vaccine encoding a set of four highly conserved MPXV surface proteins involved in virus attachment, entry, and transmission can induce MPXV-specific immunity and heterologous protection against a lethal vaccinia virus (VACV) challenge. Compared with modified vaccinia virus Ankara (MVA), which forms the basis for the current MPXV vaccine, immunization with an mRNA-based MPXV vaccine generated superior neutralizing activity against MPXV and VACV and more efficiently inhibited spread between cells. We also observed greater Fc effector T H 1-biased humoral immunity to the four MPXV antigens encoded by the vaccine, as well as to the four VACV homologs. Single MPXV antigen-encoding mRNA vaccines provided partial protection against VACV challenge, whereas multivalent vaccines combining mRNAs encoding two, three, or four MPXV antigens protected against disease-related weight loss and death equal or superior to MVA vaccination. These data demonstrate that an mRNA-based MPXV vaccine confers robust protection against VACV.

An enzyme linked immunosorbent assay (ELISA) method was developed to analyze the assembly of a tetravalent mosaic influenza nanoparticle (NP) vaccine, Flumos-v1, consisting of hemagglutinin trimers (HAT) from H1 (A/Idaho/07/2018), H3 (A/Perth/1008/2019), HBV (Vic-B/Colorado/06/2017) and HBY (Yam-B/Phuket/3073/2013) strains. The sandwich ELISA assay used lectin from Galanthus nivalis as a universal capture reagent for all HAT strains and specific monoclonal antibody (mAb) to detect corresponding hemagglutinin antigen. The mAb binding of HATs incorporated into NPs diverged from those for single HAT solutions, resulting in inaccurate quantitation of assembled HATs. An optimized zwittergent treatment was used to fully dissociate the influenza NP and aligned binding activities in each pair of single HAT and dissociated HAT from NP. The dissociated HATs were then quantified against their corresponding HAT standard solutions for three development lots of FluMos-v1 vaccine and the assembly ratio of all four HATs was calculated. The molar ratio of different HATs incorporated into this quadrivalent NP vaccine was consistent and determined as H3:H1: HBV: HBY ∼ 1.00:0.92:0.96:0.87, which was close the expected 1:1:1:1 ratio and confirmed a proper assembling of multivalent NP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Relationships between risk perceptions, emotions, and stress are well-documented, as are interconnections between stress, emotion, and media use. During the early COVID-19 pandemic, the public responded psychologically to the threat posed by the pandemic, and frequently utilized media for information and entertainment. However, we lack a comprehensive picture of how perceived risk, emotion, stress, and media affected each other longitudinally during this time. Further, although response to the pandemic was highly politicized, research has yet to address how partisan affiliation moderated relationships between risk, emotion, stress, and media use over time. This three-wave (N = 1021) panel study assessed the interplay of risk, emotion, stress, and media use for Americans with different political affiliations between March and May of 2020. Findings indicate that perceived risk, emotion, and stress at Time 1 predicted media use at Time 2, with predictors varying by type of media. Use of entertainment media and social/mobile media predicted later stress (Time 3), but news consumption did not. Later risk perceptions (Time 3) were not influenced by media use at Time 2. The predictors and consequences of different types of media use were notably different for Republicans and Democrats. In particular, risk perceptions predicted greater news use among Democrats but greater entertainment media use among Republicans. Moreover, social/mobile media use resulted in perceiving the risks of COVID-19 as less serious for Republicans while increasing stress over time for Democrats., (© 2022 Society for Risk Analysis.)

Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these trimers from their native membrane-bound context. To assess whether glycosylation could limit these base responses, we introduced sequons encoding potential N -linked glycosylation sites (PNGSs) into base-proximal regions. Expression and antigenic analyses indicated trimers bearing six-introduced PNGSs to have reduced base recognition. Cryo-EM analysis revealed trimers with introduced PNGSs to be prone to disassembly and introduced PNGS to be disordered. Protein-base and glycan-base trimers induced reciprocally symmetric ELISA responses, in which only a small fraction of the antibody response to glycan-base trimers recognized protein-base trimers and vice versa. EM polyclonal epitope mapping revealed glycan-base trimers -even those that were stable biochemically- to elicit antibodies that recognized disassembled trimers. Introduced glycans can thus mask the protein base but their introduction may yield neo-epitopes that dominate the immune response., Competing Interests: NIH has submitted a PCG patent application (PCT/US2023/065009) for Env trimers described in this manuscript on which A.S.O., C.C., T.Z., D.H.R., A.C., R.R., Y.Y., and P.D.K. are co-inventors. The other authors declare no competing interests.

Physical inactivity has become an increasingly important concern for public health. "Fitspiration" social media posts may influence attitudes and intentions toward exercising. An online survey ( N = 485) was conducted to examine the potential for fitspiration content from weak and strong ties to shape user emotions, attitudes, norms and behaviors related to exercising. Guided by the theory of planned behavior (TPB) and social cognitive theory (SCT), the results show that exposure to fitspiration content from both strong ties and weak ties were significant predictors of particular attitudes, norms, intentions, actual exercise frequency. However, our path analyses reveal significant indirect paths between exposure to fitspiration content and outcomes for weak ties through negative emotions (guilt), but only through positive emotions (hope and curiosity) for strong ties. Additionally, we found evidence that body satisfaction levels do matter in shaping the interrelationships between exposure to fitspiration content, emotions, and our outcome variables. In light of our results, we encourage researchers to consider the inclusion of emotional responses as antecedents to TPB outcomes and for practitioners to consider the role of source in campaign design.

To capture the structure of assembled hemagglutinin (HA) nanoparticles at single-particle resolution, HA-specific antigen binding fragments (Fabs) were labeled by fluorescent (FLR) dyes as probes to highlight the HA trimers displayed on the assembled tetravalent HA nanoparticles for a qualitative localization microscopic study. The FLR dyes were conjugated to the Fabs through N -hydroxysuccinimide (NHS) ester mediated amine coupling chemistry. The labeling profile, including labeling ratio, distribution, and site-specific labeling occupancy, can affect the imaging results and introduce inconsistency. To evaluate the labeling profile so as to evaluate the labeling efficiency, a combination of intact mass measurement by MALDI-MS and peptide mapping through LC-MS/MS was implemented. At the intact molecular level, the labeling ratio and distribution were determined. Through peptide mapping, the labeled residues were identified and the corresponding site-specific labeling occupancy was measured. A systematic comparative investigation of four different FLR-labeled 1H01-Fabs (generated from H1 strain HA specific mAb 1H01) allowed accurate profiling of the labeling pattern. The data indicate that the labeling was site-specific and semiquantitative. This warrants the consistency of single-particle fluorescent imaging experiments and allows a further imaging characterization of the single nanoparticles.

Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 μg of H1ssF once ( n  = 5) or 60 μg of H1ssF twice ( n  = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-μg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site ( n  = 10, 19%), headache ( n  = 10, 19%), and malaise ( n  = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine.

The scarcity of tampons in China has attracted scholarly attention. Extending the theory of planned behavior with social network structure, this cross-sectional online survey ( N  = 763) found that exposure to tampon-related information on social media was positively related to Chinese women's tampon use intentions. This association was mediated through attitudes, descriptive norms, and self-efficacy toward using tampons. Furthermore, the effects of social media exposure differed among people with different network structures. Our findings shed light on the promotion of nonconventional feminine hygiene products, which, in turn, may enhance Chinese women's well-being and gender equity across the globe.

Background: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults., Methods: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10 10 or 1 × 10 11 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056., Findings: Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10 10 pu (n=20) or 1 × 10 11 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1 × 10 10 pu group and 545 [276-1078] in the 1 × 10 11 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1 ×10 10 pu group and 27 [95-156] in the 1 ×10 11 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination., Interpretation: This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions., Funding: National Institutes of Health., Competing Interests: Declaration of interests NJS is listed on patents involving cAd3-vectored vaccines. All other authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Conjugate-vaccine immunogens require three components: a carrier protein, an antigen, and a crosslinker, capable of coupling antigen to carrier protein, while preserving both T-cell responses from carrier protein and B-cell responses from antigen. We previously showed that the N-terminal eight residues of the HIV-1 fusion peptide (FP8) as an antigen could prime for broad cross-clade neutralizing responses, that recombinant heavy chain of tetanus toxin (rTTHC) as a carrier protein provided optimal responses, and that choice of crosslinker could impact both antigenicity and immunogenicity. Here, we delve more deeply into the impact of varying the linker between FP8 and rTTHC. In specific, we assessed the physical properties, the antigenicity, and the immunogenicity of conjugates for crosslinkers ranging in spacer-arm length from 1.5 to 95.2 Å, with varying hydrophobicity and crosslinking-functional groups. Conjugates coupled with different degrees of multimerization and peptide-to-rTTHC stoichiometry, but all were well recognized by HIV-fusion-peptide-directed antibodies VRC34.01, VRC34.05, PGT151, and ACS202 except for the conjugate with the longest linker (24-PEGylated SMCC; SM(PEG)24), which had lower affinity for ACS202, as did the conjugate with the shortest linker (succinimidyl iodoacetate; SIA), which also had the lowest peptide-to-rTTHC stoichiometry. Murine immunizations testing seven FP8-rTTHC conjugates elicited fusion-peptide-directed antibody responses, with SIA- and SM(PEG)24-linked conjugates eliciting lower responses than the other five conjugates. After boosting with prefusion-closed envelope trimers from strains BG505 clade A and consensus clade C, trimer-directed antibody-binding responses were lower for the SIA-linked conjugate; elicited neutralizing responses were similar, however, though statistically lower for the SM(PEG)24-linked conjugate, when tested against a strain especially sensitive to fusion-peptide-directed responses. Overall, correlation analyses revealed the immunogenicity of FP8-rTTHC conjugates to be negatively impacted by hydrophilicity and extremes of length or low peptide-carrier stoichiometry, but robust to other linker parameters, with several commonly used crosslinkers yielding statistically indistinguishable serological results.

Background: New approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed., Methods: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria. The participants received L9LS either intravenously or subcutaneously at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight. Within 2 to 6 weeks after the administration of L9LS, both the participants who received L9LS and the control participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying Plasmodium falciparum (3D7 strain)., Results: No safety concerns were identified. L9LS had an estimated half-life of 56 days, and it had dose linearity, with the highest mean (±SD) maximum serum concentration (C max ) of 914.2±146.5 μg per milliliter observed in participants who had received 20 mg per kilogram intravenously and the lowest mean C max of 41.5±4.7 μg per milliliter observed in those who had received 1 mg per kilogram intravenously; the mean C max was 164.8±31.1 in the participants who had received 5 mg per kilogram intravenously and 68.9±22.3 in those who had received 5 mg per kilogram subcutaneously. A total of 17 L9LS recipients and 6 control participants underwent controlled human malaria infection. Of the 17 participants who received a single dose of L9LS, 15 (88%) were protected after controlled human malaria infection. Parasitemia did not develop in any of the participants who received 5 or 20 mg per kilogram of intravenous L9LS. Parasitemia developed in 1 of 5 participants who received 1 mg per kilogram intravenously, 1 of 5 participants who received 5 mg per kilogram subcutaneously, and all 6 control participants through 21 days after the controlled human malaria infection. Protection conferred by L9LS was seen at serum concentrations as low as 9.2 μg per milliliter., Conclusions: In this small trial, L9LS administered intravenously or subcutaneously protected recipients against malaria after controlled infection, without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 614 ClinicalTrials.gov number, NCT05019729.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Advances in therapeutic drugs have increased life-expectancies for HIV-infected individuals, but the need for an effective vaccine remains. We assessed safety and immunogenicity of HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in HIV-negative adults., Methods: We conducted a phase I, randomized, open-label, dose-escalation trial at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Eligible participants were HIV-negative, healthy adults between 18-50 years. Participants were randomized 1:1 to receive Trimer 4571 adjuvanted with 500 mcg alum by either the subcutaneous (SC) or intramuscular (IM) route at weeks 0, 8, and 20 in escalating doses of 100 mcg or 500 mcg. The primary objectives were to evaluate the safety and tolerability of Trimer 4571 with a secondary objective of evaluating vaccine-induced antibody responses. The primary and safety endpoints were evaluated in all participants who received at least one dose of Trimer 4571. Trial results were summarized using descriptive statistics. This trial is registered at ClinicalTrials.gov, NCT03783130., Findings: Between March 7 and September 11, 2019, 16 HIV-negative participants were enrolled, including six (38%) males and ten (62%) females. All participants received three doses of Trimer 4571. Solicited reactogenicity was mild to moderate in severity, with one isolated instance of severe injection site redness (6%) following a third 500 mcg SC administration. The most commonly reported solicited symptoms included mild injection site tenderness in 14 (88%) and mild myalgia in six (38%) participants. The most frequent unsolicited adverse event attributed to vaccination was mild injection site pruritus in six (38%) participants. Vaccine-induced seropositivity occurred in seven (44%) participants and resolved in all but one (6%). No serious adverse events occurred. Trimer 4571-specific binding antibodies were detected in all groups two weeks after regimen completion, primarily focused on the glycan-free trimer base. Neutralizing antibody activity was limited to the 500 mcg dose groups., Interpretation: Trimer 4571 was safe, well tolerated, and immunogenic in this first-in-human trial. While this phase 1 trial is limited in size, our results inform and support further evaluation of prefusion-stabilized HIV-1 envelope trimers as a component of vaccine design strategies to generate broadly neutralizing antibodies against HIV-1., Funding: Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health., Competing Interests: CC, HG, JRM, and PDK are listed on patent applications involving Trimer 4571. All other authors declare no competing interests., (© 2022 The Authors.)

Given the vast amounts of COVID-19-related messages flooding mediated and interpersonal communication channels during the global pandemic, celebrity COVID-19 disclosures offer rare opportunities to cut through message fatigue and apathy and garner the attention of wide swaths of the public. We conducted a convergent mixed method analysis of audience responses to actor Tom Hanks' March 11, 2020 disclosure of his COVID-19 diagnosis via social media. We collected our data within 24 hours of his announcement, allowing us to quickly capture emotional and cognitive responses to the announcement and to assess both demographic and psychosocial differences in types of people who heard the news in this time frame and those who had not. In our study, 587 participants had heard the news of Hanks' disclosure while 95 had not. Participants who had heard responded to an open-ended prompt asking if the disclosure affected them at all. Those who had not heard were funneled into a field intervention to test how random assignment to seeing Hanks' disclosure post or not would affect audiences' COVID-19-related emotions, cognitions, and willingness to enact prevention behaviors. The results of this mixed methods study revealed differences in responses to Hanks' disclosure based on health information source trust and involvement with Hanks as well as effects of the intervention on efficacy for dealing with COVID-19. We discuss implications for health communication theory and crafting messages that can effectively build off the attentional inertia generated by celebrity illness disclosures to encourage prevention efforts.

CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to play a key role for antibody biological activity. More importantly, here wedescribe for the first time the significance of the tyrosine-O-sulfation proteoforms. We developed a hydrophobic interaction chromatography (HIC) method to separate and quantify different sulfation proteoforms, which led to the direct functionality assessment of tyrosine-sulfated species. The fully sulfated (4-SO 3 ) proteoform demonstrated the highest in vitro relative antigen binding potency and neutralization efficiency against a panel of HIV-1 viruses. Interestingly, highly variable levels of 4-SO 3 were produced by different clonal CHO cell lines, which helped the bNAb process development towards production of a highly potent CAP256V2LS clinical product with high 4-SO 3 proteoform. This study presents powerful insight for any biotherapeutic protein development where sulfation may play an important role in product efficacy., (© 2022. The Author(s).)

Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusions of bnAbs. In this study, we administered a recombinant bicistronic adeno-associated virus (AAV8) vector coding for both the light and heavy chains of the potent broadly neutralizing HIV-1 antibody VRC07 (AAV8-VRC07) to eight adults living with HIV. All participants remained on effective anti-retroviral therapy (viral load (VL) <50 copies per milliliter) throughout this phase 1, dose-escalation clinical trial ( NCT03374202 ). AAV8-VRC07 was given at doses of 5 × 10 10 , 5 × 10 11 and 2.5 × 10 12 vector genomes per kilogram by intramuscular (IM) injection. Primary endpoints of this study were to assess the safety and tolerability of AAV8-VRC07; to determine the pharmacokinetics and immunogenicity of in vivo VRC07 production; and to describe the immune response directed against AAV8-VRC07 vector and its products. Secondary endpoints were to assess the clinical effects of AAV8-VRC07 on CD4 T cell count and VL and to assess the persistence of VRC07 produced in participants. In this cohort, IM injection of AAV8-VRC07 was safe and well tolerated. No clinically significant change in CD4 T cell count or VL occurred during the 1-3 years of follow-up reported here. In participants who received AAV8-VRC07, concentrations of VRC07 were increased 6 weeks (P = 0.008) and 52 weeks (P = 0.016) after IM injection of the product. All eight individuals produced measurable amounts of serum VRC07, with maximal VRC07 concentrations >1 µg ml -1 in three individuals. In four individuals, VRC07 serum concentrations remained stable near maximal concentration for up to 3 years of follow-up. In exploratory analyses, neutralizing activity of in vivo produced VRC07 was similar to that of in vitro produced VRC07. Three of eight participants showed a non-idiotypic anti-drug antibody (ADA) response directed against the Fab portion of VRC07. This ADA response appeared to decrease the production of serum VRC07 in two of these three participants. These data represent a proof of concept that adeno-associated viral vectors can durably produce biologically active, difficult-to-induce bnAbs in vivo, which could add valuable new tools to the fight against infectious diseases., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background and Objectives: Because of high skin cancer risks for young women, it is vital that effective interventions reach and influence this demographic. Visual social media platforms, like Instagram, are popular with young women and are an appropriate intervention site; yet, they also host competing images idealizing tan skin. The present study tested the ability of digital sun-safety interventions to affect self-control-related emotions and visual attention to subsequent tan-ideal images as well as sun-safety attitudes., Methods: Women were recruited from a large public Mid-Atlantic university in the United States. Participants ( N  = 120) were randomly assigned to view an appearance benefits intervention, a self-control emotions intervention, or a control message, each designed to look like an Instagram sponsored story. After self-reporting self-compassion and anticipated pride, participants then viewed seven pairs of Instagram posts featuring either tan or pale women while an eye tracker assessed visual attention. Finally, participants self-reported their responses to questions assessing sun-safety-related norms, efficacy, and attitudes., Results: A mixed design analysis of covariance revealed that women who first viewed the appearance benefits intervention story spent less time visually fixated on Instagram images of tan women than did those who viewed the self-control emotions intervention or control message ( p  = 0.005, η p 2  = 0.087). Regressions also revealed interactions between the intervention conditions and feelings of anticipated pride on both visual attention and sun-safety attitudes., Conclusion: Sponsored stories on Instagram can promote sun-safety attitudes, depending on the emotional responses they generate. Additionally, sponsored interventions can affect subsequent visual attention., Competing Interests: CD joined Ketchum, Inc. after data collection was complete. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Myrick, Waldron, Cohen, DiRusso, Shao, Cho, Willoughby and Turrisi.)

Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. The H2 subtype has not circulated in humans since 1968. Adults born after 1968 have been exposed to only the H1 subtype of group 1 influenza viruses, which shares a conserved stem with H2. Including both H2-naive and H2-exposed adults in the trial allowed us to evaluate memory responses against the conserved stem domain in the presence or absence of pre-existing responses against the immunodominant HA head domain. Fifty healthy participants 18-70 years of age received H2HA-Ferritin intramuscularly as a single 20-μg dose (n = 5) or a 60-μg dose either twice in a homologous (n = 25) prime-boost regimen or once in a heterologous (n = 20) prime-boost regimen after a matched H2 DNA vaccine prime. The primary objective of this trial was to evaluate the safety and tolerability of H2HA-Ferritin either alone or in prime-boost regimens. The secondary objective was to evaluate antibody responses after vaccination. Both vaccines were safe and well tolerated, with the most common solicited symptom being mild headache after both H2HA-Ferritin (n = 15, 22%) and H2 DNA (n = 5, 25%). Exploratory analyses identified neutralizing antibody responses elicited by the H2HA-Ferritin vaccine in both H2-naive and H2-exposed populations. Furthermore, broadly neutralizing antibody responses against group 1 influenza viruses, including both seasonal H1 and avian H5 subtypes, were induced in the H2-naive population through targeting the HA stem. This ferritin nanoparticle vaccine technology represents a novel, safe and immunogenic platform with potential application for pandemic preparedness and universal influenza vaccine development., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Purpose: Exposure to different types of vaccine information in social media can result in parents making disparate vaccine decisions, including not following national guidelines for human papillomavirus (HPV) vaccination. We sought to characterize parents' exposure to and engagement with information about HPV vaccination in social media, and the associations between exposure to such information and vaccine decisions for their adolescent children., Methods: In 2019, we conducted a web-based survey with a national sample of 1073 parents of adolescents who use social media. The survey assessed whether parents have seen information in favor, against, or mixed about HPV vaccination. Multivariable logistic regressions assessed correlates of vaccine decisions, including HPV vaccine initiation, delay, and refusal., Results: Sixty-one percent of parents reported that their children have initiated HPV vaccination. Over one-third of parents (37%) reported seeing HPV vaccine information on social media, which was either in favor (20%), against (5%), or a mix (12%). Parents exposed to information in favor were more likely than those who saw no information to have initiated HPV vaccination (OR = 1.74, 95% CI:1.24, 2.44). Parents exposed to information against vaccination were more likely to have delayed (OR = 3.29, 95% CI:1.66, 6.51) or refused (OR = 4.72, 95% CI:2.35, 9.50) HPV vaccination. Exposure to mixed information was also significantly associated with vaccine delay and refusal., Discussion: Our findings suggest that the type of information seen on social media regarding HPV vaccination may influence the decisions parents make about vaccinating their children. Efforts should be sought to increase online information in favor of HPV vaccination and combat vaccine misinformation in social media.

Background: Knowledge of its potential cancer risk is often not enough to motivate individuals to avoid indoor tanning. Previous research has found that emotions toward indoor tanning and appearance motivations may prompt people to continue despite the risks., Methods: We conducted two online surveys of US young adult women. Study one included a convenience sample of female undergraduates (N = 502) at a university in the northwestern USA. Study two included young women from a nationwide US online panel (N = 270)., Results: Results suggest that emotional associations, both positive and negative, with indoor tanning explain greater variances in indoor tanning behavior than demographics and previously established psychosocial predictors of tanning alone. Appearance motivations were also positively associated with indoor tanning in both samples., Conclusions: This research has implications for health care providers and health communicators, as indoor tanning prevention messages and campaigns should consider the association between both positive and negative emotions on tanning behaviors as well as appearance motivations., (© 2021. International Society of Behavioral Medicine.)

Small nucleolar (sno)RNAs guide posttranscriptional modifications essential for the biogenesis and function of their target. The majority of snoRNAs in higher eukaryotes are encoded within introns. They are first released from nascent transcripts in the form of a lariat and rapidly targeted by the debranching enzyme and nuclear exonucleases for linearization and further trimming. In this study, we report that some snoRNAs are encoded within unusually stable intronic RNAs. These intronic sequences can escape the debranching enzyme and accumulate as lariats. Stable lariats bearing a snoRNA, or slb-snoRNA, are associated with snoRNA binding proteins but do not guide posttranscriptional modification. While most slb-snoRNAs accumulate in the nucleus, some can be exported to the cytoplasm. We find that this export competes with snoRNA maturation. Slb-snoRNAs provide a previously unknown layer of regulation to snoRNA and snoRNA binding proteins., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

In eukaryotes, rRNAs and spliceosomal snRNAs are heavily modified post-transcriptionally. Pseudouridylation and 2'- O -methylation are the most abundant types of RNA modifications. They are mediated by modification guide RNAs, also known as small nucleolar (sno)RNAs and small Cajal body-specific (sca)RNAs. We used yeast and vertebrate cells to test guide activities predicted for a number of snoRNAs, based on their regions of complementarity with rRNAs. We showed that human SNORA24 is a genuine guide RNA for 18S-Ψ609, despite some noncanonical base-pairing with its target. At the same time, we found quite a few snoRNAs that have the ability to base-pair with rRNAs and can induce predicted modifications in artificial substrate RNAs, but do not modify the same target sequence within endogenous rRNA molecules. Furthermore, certain fragments of rRNAs can be modified by the endogenous yeast modification machinery when inserted into an artificial backbone RNA, even though the same sequences are not modified in endogenous yeast rRNAs. In Xenopus cells, a guide RNA generated from scaRNA, but not from snoRNA, could induce an additional pseudouridylation of U2 snRNA at position 60; both guide RNAs were equally active on a U2 snRNA-specific substrate in yeast cells. Thus, post-transcriptional modification of functionally important RNAs, such as rRNAs and snRNAs, is highly regulated and more complex than simply strong base-pairing between a guide RNA and substrate RNA. We discuss possible regulatory roles for these unexpected modifications., (© 2021 Deryusheva et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Background: Multiple active vaccination approaches have proven ineffective in reducing the substantial morbidity and mortality caused by respiratory syncytial virus (RSV) in infants and older adults (aged ≥65 years). A vaccine conferring a substantial and sustainable boost in neutralising activity is required to protect against severe RSV disease. To that end, we evaluated the safety and immunogenicity of DS-Cav1, a prefusion F subunit vaccine., Methods: In this randomised, open-label, phase 1 clinical trial, the stabilised prefusion F vaccine DS-Cav1 was evaluated for dose, safety, tolerability, and immunogenicity in healthy adults aged 18-50 years at a single US site. Participants were assigned to receive escalating doses of either 50 μg, 150 μg, or 500 μg DS-Cav1 at weeks 0 and 12, and were randomly allocated in a 1:1 ratio within each dose group to receive the vaccine with or without aluminium hydroxide (AlOH) adjuvant. After 71 participants had been randomised, the protocol was amended to allow some participants to receive a single vaccination at week 0. The primary objectives evaluated the safety and tolerability at every dose within 28 days following each injection. Neutralising activity and RSV F-binding antibodies were evaluated from week 0 to week 44 as secondary and exploratory objectives. Safety was assessed in all participants who received at least one vaccine dose; secondary and exploratory immunogenicity analysis included all participants with available data at a given visit. The trial is registered with ClinicalTrials.gov, NCT03049488, and is complete and no longer recruiting., Findings: Between Feb 21, 2017, and Nov 29, 2018, 244 participants were screened for eligibility and 95 were enrolled to receive DS-Cav1 at the 50 μg (n=30, of which n=15 with AlOH), 150 μg (n=35, of which n=15 with AlOH), or 500 μg (n=30, of which n=15 with AlOH) doses. DS-Cav1 was safe and well tolerated and no serious vaccine-associated adverse events deemed related to the vaccine were identified. DS-Cav1 vaccination elicited robust neutralising activity and binding antibodies by 4 weeks after a single vaccination (p<0·0001 for F-binding and neutralising antibodies). In analyses of exploratory endpoints at week 44, pre-F-binding IgG and neutralising activity were significantly increased compared with baseline in all groups. At week 44, RSV A neutralising activity was 3·1 fold above baseline in the 50 μg group, 3·8 fold in the 150 μg group, and 4·5 fold in the 500 μg group (p<0·0001). RSV B neutralising activity was 2·8 fold above baseline in the 50 μg group, 3·4 fold in the 150 μg group, and 3·7 fold in the 500 μg group (p<0·0001). Pre-F-binding IgG remained significantly 3·2 fold above baseline in the 50 μg group, 3·4 fold in the 150 μg group, and 4·0 fold in the 500 μg group (p<0·0001). Pre-F-binding serum IgA remained 4·1 fold above baseline in the 50 μg group, 4·3 fold in the 150 μg group, and 4·8 fold in the 500 μg group (p<0·0001). Although a higher vaccine dose or second immunisation elicited a transient advantage compared with lower doses or a single immunisation, neither significantly impacted long-term neutralisation. There was no long-term effect of dose, number of vaccinations, or adjuvant on neutralising activity., Interpretation: In this phase 1 study, DS-Cav1 vaccination was safe and well tolerated. DS-Cav1 vaccination elicited a robust boost in RSV F-specific antibodies and neutralising activity that was sustained above baseline for at least 44 weeks. A single low-dose of pre-F immunisation of antigen-experienced individuals might confer protection that extends throughout an entire RSV season., Funding: The National Institutes of Allergy and Infectious Diseases., Competing Interests: Declaration of interests MC and BSG are inventors on patents for the stabilisation of the RSV F protein. The other authors declared no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Additional interventions are needed to reduce the morbidity and mortality caused by malaria., Methods: We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with Plasmodium falciparum . Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying P. falciparum sporozoites 4 to 36 weeks after administration of CIS43LS., Results: A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 μg per milliliter at the time of controlled human malaria infection., Conclusions: Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.)., (Copyright © 2021 Massachusetts Medical Society.)

Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19., (© 2021 Bizarro et al.; Published by Cold Spring Harbor Laboratory Press.)

Purpose: Because rural residents, particularly those near mining sites, are susceptible to numerous environmental health hazards, it is important to gain deeper insights into their use and trust of health information, which they may employ to help recognize symptoms, learn ways to reduce exposure, or find health care., Methods: We surveyed residents (N = 101) of rural Kentucky, Virginia, and West Virginia to assess predictors of health information source use and trust. A project manager administered face-to-face paper and pencil questionnaires assessing demographics, health status, smoking behavior, and health information use and source trust. Bivariate correlations and ordinary least squares regressions were used to analyze the data., Findings: The data suggest that rural individuals frequently use nurses, doctors, and websites to seek health information, whereas traditional media are often not their preferred channel for health information. Media sources were not found as trustworthy as interpersonal and medical health information sources. While only 13.0% of individuals in the sample said they ever turned to county or state health departments for health information, these sources were trusted more than any media source and more than friends. Moreover, living closer to active mining sites-meaning these individuals are at a higher risk of environmental health hazards-predicted even less use of traditional media and greater trust in peer sources., Conclusions: Not all sources of health information are equally used or trusted by individuals from a rural disparities population. The findings have implications for health campaign message dissemination and intervention designs targeting individuals in rural Appalachia., (© 2021 National Rural Health Association.)

Rationale: On March 11, 2020, actor Tom Hanks announced via social media that he had been diagnosed with COVID-19. Previous research has found celebrity illness disclosures to influence behavior, but during the uncertainty of a pandemic, the effects of such a disclosure were unclear., Objective: To test the proposed Celebrity Illness Disclosure Effects (CIDE) model, demonstrating how an illness disclosure, communicated through mediated and interpersonal channels, may shape willingness to engage in prevention behaviors., Methods: We conducted an online survey (N = 587) 24 hours after Hanks' COVID-19 disclosure., Results: Findings revealed that celebrity-related perception variables predicted illness-related cognitions and emotions\, which were associated with willingness to enact prevention behaviors. Greater willingness to seek information, stronger perceptions of COVID as a threat, and stronger perceptions of efficacy for dealing with COVID after learning of Hanks' diagnosis predicted stronger willingness to enact prevention behaviors. However, anxiety about COVID predicted lower willingness to enact prevention behaviors., Conclusions: The CIDE model can serve as a guide for future research in this area. The results can help scholars who aim to better understand the phenomena around celebrities and health communication as well as policymakers who hope to ride the wave of star power to improved public health outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The lampbrush chromosomes (LBCs) in oocytes of the Mexican axolotl (Ambystoma mexicanum) were identified some time ago by their relative lengths and predicted centromeres, but they have never been associated completely with the mitotic karyotype, linkage maps or genome assembly. We identified 9 of the axolotl LBCs using RNAseq to identify actively transcribed genes and 13 BAC (bacterial artificial clone) probes containing pieces of active genes. Using read coverage analysis to find candidate centromere sequences, we developed a centromere probe that localizes to all 14 centromeres. Measurements of relative LBC arm lengths and polymerase III localization patterns enabled us to identify all LBCs. This study presents a relatively simple and reliable way to identify each axolotl LBC cytologically and to anchor chromosome-length sequences (from the axolotl genome assembly) to the physical LBCs by immunostaining and fluorescence in situ hybridization. Our data will facilitate a more detailed transcription analysis of individual LBC loops., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Here we describe novel spherical structures that are induced by cold shock on the lampbrush chromosomes (LBCs) of Xenopus laevis oocytes. We call these structures cold bodies or C-bodies. C-bodies are distributed symmetrically on homologous LBCs, with a pattern similar to that of 5S rDNA. Neither active transcription nor translation is necessary for their formation. Similar protrusions occur on the edges of some nucleoli. Endogenous LBCs as well as those derived from injected sperm form C-bodies under cold shock conditions. The function of C-bodies is unknown., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To date, there has been relatively little published research on the mental health impacts of COVID-19 for the general public at the beginning of the U.S.' experience of the pandemic, or the factors associated with stress, anxiety, depression, and post-traumatic growth during this time. The current study provides a longitudinal examination of the predictors of self-reported stress, anxiety, depression, and post-traumatic growth for U.S. residents between April and May, 2020, including the influence of demographic, psychosocial, and behavioral factors on these outcomes. The findings indicate that, generally, the early months of the U.S. COVID-19 experience were characterized by a modest negative impact on mental health. Younger adults, people with pre-existing health conditions, and those experiencing greater perceived risk, higher levels of rumination, higher levels of co-rumination, greater social strain, or less social support reported worse mental health. Positive mental health was associated with the adoption of coping strategies, especially those that were forward-looking, and with greater adherence to national health-protection guidelines. The findings are discussed with regard to the current status of health-protective measures and mental health in the U.S., especially as these impact future management of the on-going pandemic.

Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP-HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of exaggerated PP-HTG on RCT efficacy remains indeterminate. Healthy male volunteers ( n = 78) exhibiting no clinical features of metabolic disorders underwent a postprandial exploration following consumption of a typical Western meal providing 1200 kcal. Subjects were stratified according to maximal nonfasting TG levels reached after ingestion of the test meal into subjects with a desirable PP-TG response (G Low , TG < 1.8 g/L, n = 47) and subjects with an undesirable PP-TG response (G High , TG > 1.8 g/L, n = 31). The impact of the degree of PP-TG response on major steps of RCT pathway, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein (CETP) activity, and hepatic high-density lipoprotein (HDL)-cholesteryl ester (CE) selective uptake, was evaluated. Cholesterol efflux from human macrophages was not significantly affected by the degree of the PP-TG response. Postprandial increase in CETP-mediated CE transfer from HDL to triglyceride-rich lipoprotein particles, and more specifically to chylomicrons, was enhanced in G High vs G Low . The hepatic HDL-CE delivery was reduced in subjects from G High in comparison with those from G Low . Undesirable PP-TG response induces an overall reduction in RCT efficacy that contributes to the onset elevation of both fasting and nonfasting TG levels and to the development of cardiometabolic diseases.

The synaptonemal complex (SC) is a tripartite protein scaffold that forms between homologous chromosomes during meiosis. Although the SC is essential for stable homologue pairing and crossover recombination in diverse eukaryotes, it is unknown how individual components assemble into the highly conserved SC structure. Here we report the biochemical identification of two new SC components, SYP-5 and SYP-6, in Caenorhabditis elegans. SYP-5 and SYP-6 are paralogous to each other and play redundant roles in synapsis, providing an explanation for why these genes have evaded previous genetic screens. Superresolution microscopy reveals that they localize between the chromosome axes and span the width of the SC in a head-to-head manner, similar to the orientation of other known transverse filament proteins. Using genetic redundancy and structure-function analyses to truncate C-terminal tails of SYP-5/6, we provide evidence supporting the role of SC in both limiting and promoting crossover formation., (© 2020 Hurlock et al.)

Much of the extant research on representations of mental illness in the media have focused on stigmatization. The negative effects of these stigmatizing portrayals on individuals with mental illness are serious. However, recent scholarship has identified another phenomenon in the mediated portrayal of mental illness whereby these conditions are trivialized. As opposed to stigmatizing portrayals that make people with mental illness seem violent and incompetent, media portrayals that trivialize mental illnesses often treat the symptoms of these conditions (e.g., organizational ability for people with obsessive compulsive disorder or high energy levels for people with attention-deficit/hyperactivity disorder) as benefits, thereby diminishing the seriousness of these conditions. The aim of the present study was to develop a reliable and valid scale for assessing how individuals perceive symptoms of mental illnesses as benefits (and, thereby, trivialize these illnesses). Results across three studies support the existence of a reliable and valid measure whereby symptoms demark individuals with a mental illness as receiving a benefit. By establishing this scale, researchers will be better suited to assess the potential intersections and interaction of processes related to mental illness trivialization and stigmatization, both through media portrayals and through everyday interactions.

This study investigates the role of media in shaping human papilloma virus vaccination intentions in mainland China by applying both communication and marketing-focused theoretical frameworks in order to better understand ways to increase vaccine uptake across young men and women in China. An online survey (N = 359) revealed direct effects of online information consumption on perceived scarcity of the vaccine, as well as an indirect effect via perceived influence of media on others. Scarcity perceptions, in turn, predicted vaccine attitudes and behavioral intentions. Additionally, gender differences emerged in the data. Compared with women, men's intent to be vaccinated were not high, even if they realized the vaccine shortage. Implications for theory and practice are discussed., (� The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A nationally representative sample (N = 1050) responded to a survey testing possible connections between Americans' attention to media about President Donald J. Trump's preference for fast food, their perceptions of Trump, and public perceptions and behavioral intentions regarding fast food consumption. This survey utilized measures aimed at integrating theory about audience responses to celebrity health issues with the Theory of Planned Behavior and found a significant positive relationship between attention to media about Trump's diet and perceptions that fast food is socially acceptable, as well as intentions to consume it. Some, but not all, media-related variables in the analyses were positively associated with fast food perceptions and intentions, even after controlling for demographic and psychosocial factors. Attention to media specifically about Trump's dietary habits was more often associated with fast food-related perceptions and outcomes than were other types of media attention. Additionally, having a positive parasocial relationship with Trump was positively associated with increased perceived acceptability of fast food. There were also differences in the connections between attention to media about Trump's diet, parasocial relationships with Trump, and fast food perceptions and consumption intentions for audiences with different political affiliations. For instance, attention to media about Trump in general was positively associated with more positive attitudes toward fast food for Republicans, but not for Democrats are those unaffiliated with either political party. Attention to media specifically about Trump's diet was positively related to fast food attitudes for both Republicans and Democrats but not unaffiliated individuals. This study demonstrates the important role of social, political, and media influences in shaping fast food related perceptions and preferences and offers many potential avenues for future research in this area., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

During DNA replication, the genetic information of a cell is copied. Subsequently, identical genetic information is segregated reliably to the two daughter cells through cell division. Meanwhile, DNA replication is intrinsically linked to the process of chromatin duplication, which is required for regulating gene expression and establishing cell identities. Understanding how chromatin is established, maintained or changed during DNA replication represents a fundamental question in biology. Recently, we developed a method to directly visualize chromatin components at individual replication forks undergoing DNA replication. This method builds upon the existing chromatin fiber technique and combines it with cell type-specific chromatin labeling and superresolution microscopy. In this method, a short pulse of nucleoside analog labels replicative regions in the cells of interest. Chromatin fibers are subsequently isolated and attached to a glass slide, after which a laminar flow of lysis buffer extends the lysed chromatin fibers parallel with the direction of the flow. Fibers are then immunostained for different chromatin-associated proteins and mounted for visualization using superresolution microscopy. Replication foci, or 'bubbles,' are identified by the presence of the incorporated nucleoside analog. For researchers experienced in molecular biology and superresolution microscopy, this protocol typically takes 2-3 d from sample preparation to data acquisition, with an additional day for data processing and quantification.

Small nucleolar RNAs (snoRNAs) function primarily as guide RNAs for posttranscriptional modification of rRNAs and spliceosomal snRNAs, both of which are functionally important and evolutionarily conserved molecules. It is commonly believed that snoRNAs and the modifications they mediate are highly conserved across species. However, most relevant data on snoRNA annotation and RNA modification are limited to studies on human and yeast. Here, we used RNA-sequencing data from the giant oocyte nucleus of the frog Xenopus tropicalis to annotate a nearly complete set of snoRNAs. We compared the frog data with snoRNA sets from human and other vertebrate genomes, including mammals, birds, reptiles, and fish. We identified many Xenopus-specific (or nonhuman) snoRNAs and Xenopus-specific domains in snoRNAs from conserved RNA families. We predicted that some of these nonhuman snoRNAs and domains mediate modifications at unexpected positions in rRNAs and snRNAs. These modifications were mapped as predicted when RNA modification assays were applied to RNA from nine vertebrate species: frogs X. tropicalis and X. laevis, newt Notophthalmus viridescens, axolotl Ambystoma mexicanum, whiptail lizard Aspidoscelis neomexicana, zebrafish Danio rerio, chicken, mouse, and human. This analysis revealed that only a subset of RNA modifications is evolutionarily conserved and that modification patterns may vary even between closely related species. We speculate that each functional domain in snoRNAs (half of an snoRNA) may evolve independently and shuffle between different snoRNAs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Although the nucleolus was first described in the early 19 th century from both animal and plant cells, human nucleoli and particularly the five human nucleolus organizers have not been well characterized. In this issue of Genes & Development , van Sluis and colleagues (pp. 1688-1701) present a detailed molecular analysis of these organizers, which occur on the short arms of five human chromosomes. The near identity of these arms suggests extensive interchromosomal exchange during evolutionary history., (© 2019 Gall; Published by Cold Spring Harbor Laboratory Press.)